This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Human APOBEC3G (A3G) is capable of altering the HIV genome by deaminating cDNA cytosines to uracils. This activity can genetically inactivate the virus. As a counter-defense mechanism, HIV promotes the ubiquitin-mediated protein degradation of A3G. Degradation requires that A3G interacts with the HIV virion infectivity factor (Vif) protein. Current studies have revealed substantial genetic and biochemical details of this host-pathogen conflict, but an atomic level understanding is still lacking. Therefore, the major objectives of this research are to obtain a structural understanding of the DNA cytosine deaminase activity of A3G and of the A3G-Vif interaction.